Clonal expansion in B-CLL: fungal drivers or self-service?

Abstract

Relatively few cancers arise in mature, differentiated cells. The propensity of mature B cells to transform has been linked to their longevity and proliferative potential, and stimulation of the B cell receptor (BCR) by cognate antigen may promote the transformation process. A study in this issue (Hoogeboom et al.) lends support to this notion, showing that cancer cells from a subset of patients with chronic lymphocytic leukemia (CLL) express a BCR specific for a sugar expressed by commensal yeast species. Another study, in contrast, suggests that B-CLL cells uniquely acquire the ability to signal in the complete absence of ligand.

Figure 1.

Putative pattern of clonal evolution and antigen dependence in CLL. Three potential mechanisms may underlie microbial drive in the transformation of B cells in CLL. Germinal center B cells with high-affinity BCRs (blue) may be chronically stimulated by microbial antigens, increasing the probability that the cell acquires transforming mutations. After transformation, subclones of antigen-specific B cells may acquire mutations that confer a selective proliferative advantage in the presence of antigen (orange). Finally, antigen-specific B cells may acquire mutations that render BCR signaling completely independent of antigenic ligation (green). The “Y”-shaped symbols indicate BCRs, and “A” indicates nominal antigens derived from microbial infection.